This is a competitive renewal of the Western New England Pediatric Aids Clinical Trials Unit (WNEPACTU), established in 1992 at the University of Massachusetts Medical Center, Worcester, Massachusetts, and is submitted in conjunction with the Pediatric Aids Clinical Trials Group (PACTG) Coordinating and Operations Center (CORC) application submitted by Steven Spector, M.D., UCSD. The WNEPACTU includes two subunits located at Baystate Medical Center in Springfield, Massachusetts and the University of Connecticut Health Science Center in Farmington, Connecticut. The WNEPACTU has been a national and international leader in the study of the pathogenesis of vertical HIV-1 infection. We have pioneered the development of the non-nucleoside reverse transcriptase inhibitor, nevirapine, which is the first HIV antiretroviral to be developed contemporaneously in adults and children. Investigators from WNEPACTU have assumed leadership positions in the PACTG and have played a major role in the development and accomplishment of the scientific agenda. The primary objectives of the WNEPACTU are: 1) To continue our studies aimed at understanding the pathogenesis of vertical HIV-1 infection; 2) To develop and implement perinatal intervention protocols which will further reduce vertical HIV-1 transmission in the US and be available to the developing world; 3) To develop and implement combination antiretroviral therapy protocols in early vertical infections to achieve about 90% ten year survival following vertical HIV infection. Our history of scientific contributions, performance of the WNEPACTU, and our leadership in the PACTG combined with our unique expertise to help address the scientific agenda makes the WNEPACTU an ideal site for continued membership in the Pediatric Aids Clinical Trials Group.